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Posted: Mar 06, 2007

Radical nanotechnology - how medicine can learn from materials science

(Nanowerk Spotlight) Can a major component of a catalytic converter or a fullerene derivative lead to an eventual treatment for Parkinson's disease or arthritis? Research to date certainly hints at this possibility. In chemistry, radicals (often referred to as free radicals) are atomic or molecular species with unpaired electrons on an otherwise open shell configuration. These unpaired electrons are usually highly reactive, so radicals are likely to take part in chemical reactions. Radicals play an important role in human physiology but, because of their reactivity, they also can can participate in unwanted side reactions resulting in cell damage. Free radicals damage components of the cells' membranes, proteins or genetic material by "oxidizing" them - the same chemical reaction that causes iron to rust. This is called "oxidative stress". Many forms of cancer are thought to be the result of reactions between free radicals and DNA, resulting in mutations that can adversely affect the cell cycle and potentially lead to malignancy. Oxidative stress is believed to play a role in neurodegenerative diseases such as Alzheimer's and Parkinson's.Some of the symptoms of aging such as arteriosclerosis are also attributed to free-radical induced oxidation of many of the chemicals making up the body. Despite the broad role that oxidative stress plays in human disease, medicine has been limited in its development of treatments that counteract free radical damage and the ensuing burden of oxidative stress. In contrast, in the field of engineering, considerable effort has been developed to counter the effects of oxidative stress at the materials science level. Nanotechnology has provided numerous constructs that reduce oxidative damage in engineering applications with great efficiency. A recent review looks at how these nanoengineering concepts could be applied to biomedical problems, ultimately leading to nanotechnology-based therapeutical treatments for oxidative stress-induced diseases.
"The chemical and physical processes involved in tree-way catalysis for improved combustion and removal of environmental contaminants from engine exhausts have similarities with biological redox reactions and antioxidants, from a chemical and physical standpoint" Dr. Beverly A. Rzigalinski explains to Nanowerk. "Likewise, the role of coatings on the reduction of metal oxidation involves chemical principles similar to those associated with the prevention of oxidation in biomolecules. Nanotechnology has provided dramatic improvement in controlling or eliminating oxidation reactions in materials applications. This may provide a new basis for pharmacological treatment of diseases related to oxidative stress."
Three of the most-studied nanoparticle redox reagents, at the cellular level, are rare earth oxide nanoparticles (particularly cerium), fullerenes and carbon nanotubes.
Rzigalinski, a professor at the Virginia College of Osteopathic Medicine and Virginia Polytechnic & State University, is lead author of a recent review in Future Medicine that looks at the properties of these nanoparticles and discusses their potential applications in biomedicine ("Radical nanomedicine").
"Our initial results suggest that cerium oxide nanoparticles extend cell and organism longevity through their actions as regenerative free radical scavengers" Rzigalinski summarizes the core findings of her review. "Additional studies suggest that these nanoparticles are also potent anti-inflammatory agents. Although much work remains to be done in this realm, ceria nanoparticles hold high promise for future development of nanopharmacological agents to treat age related neurodegenerative disorders and inflammatory disorders."
Research has already shown that nanoparticles composed of cerium oxide or yttrium oxide protect nerve cells from oxidative stress and that the neuroprotection is independent of particle size (see our Nanowerk Spotlight from a year ago: "Could nanoparticles be designed to become potent antioxidants?").
Several studies also suggest that ceria nanoparticles are potent anti-inflammatory agents. Most intriguingly, Rzigalinski's research shows that cerium nanoparticles directly added to the food increased maximum and average life span of fruit flies. Of course there is a long way from fruit flies to humans, but this research indicates that these particles might have antioxidative properties that, once their mechanism of action is fully understood, one day also could benefit therapeutic applications for humans.
"Our work brings future potential for nanopharmacology closer to reality" says Rzigalinski. "By designing additional ceria constructs, we hope to be able to direct and control free radical scavenging activity."
So far, the chemistry and physics of ceria nanoparticles support the hypothesis that the biological actions of ceria are related to a regenerative free radical scavenging ability. During the experiments with fruit flies it was clearly shown that a single, low dose of ceria nanoparticles protected cells from free radical damage over an extended period of time.
In contrast to ceria and other rare earth nanoparticles, several reports also describe the free radical scavenging capabilities of fullerene derivatives and carbon nanotubes. Their antioxidant activity is hypothesized to be related to the large electronegative center of these constructs (see "Fullerene-based antioxidants and neurodegenerative disorders." for a nice summary).
However, several studies also showed detrimental effects of certain functionalized fullerenes in the treatment of oxidative stress. The potential toxicity of carbon nanotubes is much debated but, nevertheless, they also have been reported to have free radical scavenging properties. Much more research needs to be done on carbon nanomaterials to determine their antioxidant properties.
Rzigalinski points out that the case for nanoparticles as free radical scavengers holds great promise for future pharmacotherapy of diseases in which oxidative stress is a component. However, these studies, as with much of nanomedicine, are in their infancy.
"Our knowledge of the physiological behavior of nanoparticles is scant and we are just starting down the road from bench to bedside – a road that will no doubt require numerous adaptations to our traditional concepts of pharmacology," Rzigalinski says.
By , Copyright Nanowerk LLC

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